Restoring Hope: Repeated Ketamine Infusions Significantly Reduce Suicidal Ideation in Veterans with PTSD and MDD

In the clinical report Improvement in suicidal ideation after repeated ketamine infusions by Albott et al. (2019), a groundbreaking finding emerged: repeated doses of intravenous ketamine led to rapid and sustained reductions in suicidal ideation (SI) among veterans suffering from both posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). This study provides strong preliminary support for ketamine’s role as a life-saving intervention in a population for whom traditional antidepressants and therapeutic interventions may fall short.

Suicidal ideation remains a major concern among individuals with co-occurring PTSD and depression. Despite increasing awareness and available treatment options, many patients experience persistent thoughts of self-harm that resist conventional therapies. This research sheds light on how ketamine’s unique neurobiological effects may provide urgently needed relief for high-risk individuals.

Study Design: Intensive and Targeted Treatment for a High-Risk Population

The study enrolled 15 U.S. military veterans diagnosed with comorbid PTSD and MDD. All participants reported active suicidal ideation at baseline, highlighting the severity of their condition.

Participants received six infusions of intravenous ketamine (0.5 mg/kg) on a Monday-Wednesday-Friday schedule over 12 days. This rapid-delivery protocol aimed to evaluate how quickly and sustainably ketamine could reduce SI in this particularly vulnerable group.

Measurement Tools and Timelines

Outcome assessments were performed immediately before and 24 hours after each infusion, tracking both psychiatric symptoms and physical pain.

Key instruments included:

• Montgomery-Åsberg Depression Rating Scale (MADRS) — assessing overall depression severity and SI via a dedicated item
• PTSD Checklist for DSM-5 (PCL-5) — evaluating key symptom clusters: intrusion, avoidance, negative mood and cognition, and hyperarousal
• Visual Analog Scale (VAS) — capturing levels of physical pain

Results: Suicidal Ideation Drops Significantly and Rapidly

Within 24 hours of the first ketamine infusion, patients exhibited a statistically significant decrease in suicidal ideation (Z = 3.21; p = .001). Even more notably, this improvement persisted across all subsequent time points, indicating both rapid and sustained relief.

By the conclusion of the infusion series, reductions in SI were strongly correlated with improvements in several PTSD symptom domains:

• Avoidance behaviors (r = .610, p = .021)
• Negative alterations in cognition/mood (r = .786, p = .001)
• Hyperarousal (r = .729, p = .003)
• Pain symptoms (r = .591, p = .013)

Importantly, these improvements in suicidality remained significant even when controlling for overall depression symptom improvement, suggesting ketamine’s SI-reducing effect may act through PTSD-specific and pain-related mechanisms, not just its antidepressant properties.

Clinical Impact: A New Pathway to Saving Lives

This study carries critical implications for clinical practice:

• Rapid reduction in suicidality: Traditional antidepressants often take weeks to produce noticeable effects. In contrast, ketamine can reduce SI within 24 hours, offering immediate reprieve.
• Multifaceted symptom improvement: Ketamine’s benefits extended beyond mood, significantly affecting PTSD symptoms and pain, which are known contributors to suicidality.
• Potential standalone anti-suicidal mechanism: Because the improvement in SI was independent of depression reduction, this suggests ketamine may uniquely target suicidality through different neural circuits or receptor systems.

Limitations and Considerations

While these findings are promising, several limitations must be acknowledged:

• Small sample size (N=15) limits generalizability.
• Lack of control group makes it difficult to rule out placebo effects.
• Short follow-up period (limited to post-infusion assessments) prevents conclusions about long-term efficacy or relapse rates.

Nevertheless, the study provides valuable preliminary evidence to support ketamine’s role in acute crisis intervention, particularly for veterans and others with complex trauma histories.

Conclusion

The study Improvement in suicidal ideation after repeated ketamine infusions underscores ketamine’s potential to offer life-saving, fast-acting relief for suicidal individuals with PTSD and MDD. By targeting the emotional, cognitive, and somatic drivers of suicidality, ketamine opens a new chapter in treating some of the most urgent and intractable symptoms in psychiatry.

As the mental health field continues to seek interventions that can respond quickly and effectively in moments of crisis, ketamine stands out as a promising option—especially when every hour counts.

References

1. Albott CS, Lim KO, Forbes MK, et al. Improvement in suicidal ideation after repeated ketamine infusions. J Clin Transl Sci. 2019;3(s1):46–46.
2. Grunebaum MF, Galfalvy HC, Choo TH, et al. Ketamine for rapid reduction of suicidal thoughts in major depression: a midazolam-controlled randomized clinical trial. Am J Psychiatry. 2018;175(4):327–335.
3. Abdallah CG, Averill LA, Krystal JH. Ketamine as a promising prototype for a new generation of rapid-acting antidepressants. Ann N Y Acad Sci. 2015;1344:66–77.
4. Feder A, Parides MK, Murrough JW, et al. Efficacy of intravenous ketamine for treatment of chronic PTSD: a randomized clinical trial. JAMA Psychiatry. 2014;71(6):681–688.

Wilkinson ST, Ballard ED, Bloch MH, et al. The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis. Am J Psychiatry. 2018;175(2):150–158.